Cell proliferation of normal human thymus-derived lymphocytes is dependent upon the presence of multiple signals. The first component is provided by an antigen (or lectin), with the second being derived from a monocyte (interleukin-1 [IL-1]). These two agents interact with the human T cell to give an eventual mitogenic response. The mechanism by which the presence of an antigen and IL-1 results in the proliferative response is thought to be due to a third, T-cell derived signal, termed interleukin-2 (IL-2). IL-2 has been shown to act as the ultimate mitogenic signal for the actual induction of T-cell proliferation. These signals provide a unique system by which to isolate G0 quiescent, G0/G1 activated, G1 progressive and log-phase normal T cells. This cell-cycle control will allow for the effective study of the early events in the induction of T-cell proliferation. Furthermore, they provide an effective system for the isolation of relatively cell cycle specific normal cell populations for comparison with malignant T cells (represented by cell lines CCRF-CEM and CCRF-HSB-2) in known cell-cycle states. These cell systems will be utilized to explore the role of specific subsets of nonhistone chromosomal proteins with respect to the induction of cell proliferation and progression of cells through the early stages of the cell cycle. Experiments will also be conducted to examine more explicitly the nature of cell cycle control in the normal T cell exposed to the proliferative signals. These studies will include an examination of the nature of T-cell subset selectivity to the interleukin signals with the goal of further understanding cell cycle-related events occurring during the induction of growth. Experiments are also proposed to study the efficacy of soluble factors in the control of human B lymphocyte proliferation, using growth-promoting agents specific for cells of this lineage (BCGF). Studies will focus on the ability to isolate human B cells in specific cell-cycle states in a manner analogous to the cycle control now capable with human T lymphocytes.